MOTS-c Peptide Reduces Lung Damage from Radiation Therapy

Radiation pneumonitis (RP) is a severe and dose-limiting complication of thoracic radiotherapy, commonly used to treat lung cancer and other chest malignancies. This debilitating condition is characterized by progressive inflammation and subsequent fibrosis in the lung tissue, leading to impaired respiratory function and significantly impacting patient quality of life and survival. Current therapeutic options for RP are largely supportive and limited in their efficacy, highlighting an urgent need for more targeted and effective interventions. This study specifically addresses the critical knowledge gap in identifying novel, mechanism-based strategies to prevent or mitigate radiation-induced lung injury.

The study revealed that MOTS-c treatment significantly attenuated radiation-induced lung injury in the mouse model. Treated mice exhibited a marked reduction in inflammatory cell infiltration and fibrosis within the lung tissue. Specifically, MOTS-c decreased the levels of key pro-inflammatory cytokines, including IL-6, TNF-α, and IL-1β, by over 50% compared to irradiated controls. Furthermore, the peptide effectively reduced oxidative stress, evidenced by a 30% decrease in malondialdehyde (MDA) and reactive oxygen species (ROS) levels, while simultaneously increasing the activity of antioxidant enzymes like superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) by approximately 2-fold. This protective effect was mediated through the activation of the Nrf2 signaling pathway, a master regulator of antioxidant responses. > MOTS-c treatment consistently led to a significant reduction in both lung inflammation and fibrosis, with histological scores and inflammatory markers demonstrating improvements with p<0.05 compared to the untreated irradiated group. Crucially, in Nrf2-knockout mice, MOTS-c failed to confer any protection against radiation pneumonitis, unequivocally demonstrating that its therapeutic benefits are dependent on the Nrf2 pathway.